Cellular Senescence

Senescent cells are present in aged tissues taken from variety of species, including mice, baboons and humans [Herbig et al. 2006; Jeyapalan et al. 2007; Wang et al 2009]. In fact tissues from aged aged animals are a mixture of senescent cells interspersed with normal cells (old, perhaps age-compromised cells but not yet senescent) [Bahar et al. 2006; Herbig et al. 2006]. The number of senescent fibroblasts increases exponentially with age in the skin of baboons. Senescent cells are over 15% of cells in very old animals [16456035]. Senescence cells are also present in mouse tissues such as in the liver [18440596].

Senescence can be triggered by several stressors that result in molecular damage or simple by exhaustion of replicative potential [Adams 2009].

Cellular senescence is characterized by biochemical events that occur with the cell leading to growth arrest as well as loss of specialized cellular functions [Campisi et al. 2002]. Senescent cells cannot divide, their ability to synthesize proteins is reduced, and the DNA repair system is attenuated [Hasty et al. 2003].

Telomere shortening with age contribute to cancer susceptibilityby increasing the risk of chromosomal aberrations [11089982]. Mice with short telomeres have higher cancer incidence [10089885], including in mice deficient for p53 [10338216].

Senescent cells secret pro-inflammatory cytokines and other factors that disrupt the tissue microenvironment and promote tumorigenesis. Immunocompromised mice injected with tumor-forming cells together with senesecent cells form more and larger tumors that tumour-forming cells alone or with presenescent cells [11593017; 20169192; 17409418]. Senescent cells derive a inflammatory network dependent of interleukins that promotes cancer [18555778].

The clearance of senescent cells expression p16INK4a, although it does not extend the lifespan, delays aging-associated disorders in progeriod mice [22048312].

Senescent human fibroblasts stimulate profileration of premalignant and malignant epithelial cells, but not of normal cells in cell culture [11593017].